Cardiac output, the volumetric rate at which blood is pumped through the heart, is most often determined clinically by injecting a bolus of chilled saline or glucose solution into the right auricle or right ventricle through a catheter. A thermistor disposed in the pulmonary artery is used to determine a temperature-time washout curve as the chilled injectate/blood mixture is pumped from the heart. The area under this curve provides an indication of cardiac output. Although this thermodilution method can give an indication of cardiac output at the time the procedure is performed, it cannot be used for continuously monitoring cardiac output. Moreover, the frequency with which the procedure is performed is limited by its adverse effects on a patient, including the dilution of the patient's blood that occurs each time the chilled fluid is injected. In addition, the procedure poses an infection hazard to medical staff from blood contact, and to the patient, from exposure to possibly contaminated injectate fluid or syringes.
Alternatively, blood in the heart can be chilled or heated in an injectateless method by a heat transfer process using a temperature-conditioned fluid that is pumped in a closed loop, toward the heart through one lumen within the catheter and back through another lumen. The principal advantages of using such a non-injectate heat transfer process to change the temperature of blood are that repetitive measurements can be performed without overloading the patient with large quantities of fluid or exposing the patient to the risk of infection.
U.S. Pat. No. 4,819,655 (Webler) discloses an injectateless method and apparatus for determining cardiac output. In Webler's preferred embodiment, a saline solution is chilled by a refrigeration system or ice bath and introduced into a catheter that has been inserted through a patient's cardiovascular system into the heart. The catheter extends through the right auricle and right ventricle and its distal end is disposed just outside the heart in the pulmonary artery. A pump forces the chilled saline solution through a closed loop fluid path defined by two lumens in the catheter, so that heat transfer occurs between the solution and blood within the heart through the walls of the catheter. A thermistor disposed at the distal end of the catheter monitors the temperature of blood leaving the heart, both before the chilled fluid is circulated through the catheter to define a baseline temperature, and after the temperature change in the blood due to heat transfer with the chilled saline solution has stabilized. Temperature sensors are also provided to monitor both the temperature of the chilled saline solution at or near the point where it enters the catheter (outside the patient's body) and the temperature of the fluid returning from the heart. In addition, the rate at which the chilled solution flows through the catheter is either measured or controlled to maintain it at a constant value. Cardiac output (CO) is then determined from the following equation: ##EQU1##
where V.sub.I equals the rate at which the chilled fluid is circulated through the catheter; .DELTA.T.sub.I equals the difference between the temperature of the chilled fluid input to the catheter and the temperature of the fluid returning from the heart; .DELTA.T.sub.B equals the difference between the temperature of the blood leaving the heart before the chilled fluid is circulated and the temperature of the blood leaving the heart after the chilled fluid is circulated (after the temperature stabilizes); and C is a constant dependent upon the blood and fluid properties. The patent also teaches that the fluid may instead be heated so that it transfers heat to the blood flowing through the heart rather than chilled to absorb heat.
U.S. Pat. No. 4,819,655 further teaches that the cardiac monitoring system induces temperature variations in the pulmonary artery that are related to the patient's respiratory cycle and are therefore periodic at the respiratory rate. Accordingly, Webler suggests that the signal indicative of T.sub.B ' (the temperature of the chilled blood exiting the heart) should be processed through a Fourier transform to yield a period and amplitude for the respiratory cycle, the period or multiples of it then being used as the interval over which to process the data to determine cardiac output.
Another problem recognized by Webler is the delay between the times at which circulation of the chilled fluid begins and the temperature of the blood in the pulmonary artery reaches equilibrium, which is caused by the volume of blood surrounding the catheter in the right ventricle and in other portions of the heart. The patent suggests introducing a generally corresponding delay between the time that temperature measurements are made of the blood before the chilled fluid is circulated and after, for example, by waiting for the T.sub.B ' value to exceed a level above that induced by respiratory variations. However, for a relatively large volume heart and/or very low cardiac output, the T.sub.B ' data do not reach equilibrium in any reasonable period of time. The quantity of blood flowing through the large volume heart represents too much mixing volume to accommodate the technique taught by Webler for processing the data to determine cardiac output. As a result, the measurement period for equilibrium must be excessively long to reach equilibrium, thereby introducing a potential error in the result due to either a shift in the baseline temperature of the blood or changes in the cardiac output. For this reason, the technique taught by Webler to determine cardiac output using the data developed by his system is not practical in the case of large blood volumes in the heart and/or low cardiac outputs.
Instead of cooling (or heating) the blood in the heart by heat transfer with a circulating fluid to determine cardiac output, the blood can be heated with an electrical resistance heater that is disposed on a catheter inserted into the heart. The apparatus required for this type of injectateless cardiac output measurement is significantly less complex than that required for circulating a fluid through the catheter. An electrical current is applied to the resistor through leads in the catheter and adjusted to develop sufficient power dissipation to produce a desired temperature rise signal in the blood. However, care must be taken to avoid using a high power that might damage the blood by overheating it. An adequate signal-to-noise ratio is instead preferably obtained by applying the electrical current to the heater at a frequency corresponding to that of the minimum noise generated in the circulatory system, i.e., in the range of 0.02 through 0.15 Hz. U.S. Pat. No. 4,236,527 (Newbower et al.) describes such a system, and more importantly, describes a technique for processing the signals developed by the system to compensate for the above-noted effect of the mixing volume in the heart and cardiovascular system of a patient, even one with a relatively large heart. (Also see J. H. Philip, M. C. Long, M. D., Quinn, and R. S. Newbower, "Continuous Thermal Measurement of Cardiac Output," IEEE Transactions on Biomedical Engineering, Vol. BMI 31, No. 5, May 1984.)
Newbower et al. teaches modulating the thermal energy added to the blood at two frequencies, e.g., a fundamental frequency and its harmonic, or with a square wave signal. Preferably, the fundamental frequency equals that of the minimal noise in the cardiac system. The temperature of the blood exiting the heart is monitored, producing an output signal that is filtered at the fundamental frequency to yield conventional cardiac output information. The other modulation frequency is similarly monitored and filtered at the harmonic frequency, and is used to determine a second variable affecting the transfer function between the injection of energy into the blood and the temperature of the blood in the pulmonary artery. The amplitude data developed from the dual frequency measurements allows the absolute heart output to be determined, thereby accounting for the variability of fluid capacity or mixing volume.
Newbower's technique for determining cardiac output requires the use of a model for the system represented by the effect of the input power on the blood temperature output signal. The data must be fit to the model to correct for mixing volume attenuation.
As an alternative to the model of Newbower, M. Yelderman has developed a method for reconstructing an impulse response for a cardiac output monitoring system using a pseudo random binary noise and cross-correlation technique. This method is described in U.S. Pat. No. 4,507,974. Yelderman teaches that any indicator may be introduced into the blood mass in the form of any stochastic or spread spectral process. For example, a catheter mounted heating filament can be energized with a stochastic or pseudo random input to supply a corresponding heat input signal to the blood in the heart. The vascular system impulse response obtained by downstream measurement and cross correlation with the input signal produces information that is then combined with a conservation of heat equation to measure volumetric fluid flow by integrating the area under the impulse response curve. Yelderman's method is prone to drift and noise being coupled into the reconstructed impulse response which makes accurate level detection and integration difficult.
One inaccuracy in prior art methods of determining cardiac output is due to thermal noise and thermal drift. Thermal drift is generally a very low frequency drift in the temperature of the blood in the heart and is due to physiological factors as opposed to the thermal energy introduced into the blood during cardiac output measurements.
One cause of thermal noise is the difference in temperature between the blood returning from different parts of the body. Fluctuating pressure gradients across the chest wall caused by respiration vary the volume of blood returning to the heart from organs outside the chest relative to the volume of blood returning from organs inside the chest. Blood returning from organs with a high metabolic rate such as the liver is hotter than blood returning from say the stomach while blood returning from the periphery is much colder depending partly on room temperature. As blood returns from different parts of the body, the temperature of the blood in the heart fluctuates, thus producing a thermal noise or thermal drift in cardiac output measurements. For example, the amount of blood entering the heart from the superior or inferior vena cava varies during each respiration cycle, thus changing the temperature of the blood in the heart. Also long term homeostatic control systems in the body cause long term slow fluctuations in mixed venous blood temperature as a result of adjusting the quantity of blood flowing to the periphery and varying the metabolic rate to try to maintain "core" temperature constant.
PCT patent WO 91/16603 (McKown) discloses a method that attempts to account for the effects of thermal drift on cardiac output measurements using Yelderman's cross-correlation technique. McKown assumes that, regardless of thermal noise or drift, the average power supplied to the blood over each measurement period and thus the average power measured during cardiac output measurements remains constant. Based on this assumption, McKown determines the average level of the resultant measured temperature signal over each of several adjacent measurement periods. In the preferred embodiment, McKown uses three measurement periods, thus producing three measurements of average signal level. A quadratic curve is then fit to the data produced by measurements of average signal level. The portion of the quadratic curve associated with the center measurement period is then subtracted from the measured cardiac output signal on a point-by-point basis in order to produce "zero mean" data, thus reducing the effects of thermal drift.
McKown's method of fitting a quadratic curve to the temperature signal fits three variables simultaneously to the noisy data. If the temperature signal is particularly noisy, such a quadratic fit can induce errors larger than those present in the uncompensated original signal. McKown's method requires at least two adjacent measurement periods to be completed prior to accounting for the effect of thermal drift. If the quadratic fit is inaccurate due to short term noise during one measurement period errors in output measurements due to that noisy period propagate to adjacent measurement periods as well, since the quadratic fit is repeated for each period using overlapping adjacent averages. This results in three inaccurate measurements instead of one. In addition, because McKown's method requires at least three measurement periods to be completed before cardiac output can be determined, there is a longer lag time between the occurrence of the cardiac event being measured and subsequent data output. This lag time prevents an operator from observing the cardiac output in real time, possibly affecting the patient's treatment. Due to measurement errors induced by signal-to-noise ratios and attenuation, the measurement time period can not generally be reduced much below 30 seconds. Thus, the results of a cardiac output measurement produced by the method of McKown would be delayed by an additional one and perhaps, up to two minutes after the cardiac event and the effects of transient noise would more likely be coupled into multiple measurements.
T. Hughes in U.S. Pat. No. 5,261,411 describes methods of reducing drift in cardiac output determinations by adjusting the starting point of the measurement period for each harmonic used so that the signal in the frequency domain has only a Real component of the input signal used. This is more complex to implement and can give rise to a small variable delay in update time. T. Hughes and D. Swingler in U.S. Pat. No. 5,363,856 describe methods for reducing drift in cardiac output determinations by shifting and adding the thermal signal to itself so as to leave only the drift signal and then identifying the drift slope by regression techniques. This allows drift removal within a single period of the input signal but is complex requiring robust regression techniques to be used in the presence of non-Gaussian thermal noise.
A goal of the present invention is to provide a method and apparatus for reducing the effects of thermal drift on measurements of cardiac output while reducing some of the problems associated with the prior art, including maintaining a short lag time required to determine cardiac output while minimizing the effects of noise.